关键词: Wnt antiviral miR-181a miR-192 microRNA rotavirus β-Catenin Wnt antiviral miR-181a miR-192 microRNA rotavirus β-Catenin

Mesh : Cell Line, Tumor Cell Proliferation MicroRNAs / genetics metabolism Prospective Studies Rotavirus / genetics metabolism Wnt Signaling Pathway / physiology beta Catenin / genetics metabolism

来  源:   DOI:10.3390/v14030558

Abstract:
The significance of the Wnt/β-catenin signaling cascade in Rotavirus (RV) infection has not been elucidated. In this study, we attempt to elucidate the importance of the Wnt/β-catenin pathway in the RV pathogenesis and investigate a miRNA-mediated approach to regulate the pathway to repress the RV infection in the host. The regulation of the Wnt signaling pathway in terms of β-catenin accumulation and activation was analyzed by Western blotting and Confocal imaging analysis. The expression levels of miR-192 family members and miR-181a were enquired into using qPCR assays, whereas their targets in the Wnt pathway were confirmed using the Luciferase Reporter Assays. Members of the miR-192 family and miR-181a, which target the components of the pathway, were also found to be considerably decreased in expression during RV infection. Ectopic expression of these miRNAs could restrict the RV pathogenesis by targeting the intermediates of the Wnt signaling pathway. The miR-192 family and miR-181a were capable of suppressing the RV infection via targeting of the Wnt/β-catenin pathway. The study not only highlights the role of the Wnt signaling cascade in RV infection but also suggests that miRNAs can synergistically decrease RV replication by a significant amount. Thus, the miR-192 family and miR-181a present themselves as prospective antivirals against RV infection.
摘要:
尚未阐明轮状病毒(RV)感染中Wnt/β-连环蛋白信号级联的重要性。在这项研究中,我们试图阐明Wnt/β-catenin通路在RV发病机制中的重要性,并研究一种miRNA介导的调节途径以抑制宿主RV感染.通过Western印迹和共聚焦成像分析来分析Wnt信号通路在β-连环蛋白积累和活化方面的调节。使用qPCR检测miR-192家族成员和miR-181a的表达水平,而它们在Wnt途径中的靶标使用荧光素酶报告基因测定来证实。miR-192家族成员和miR-181a,靶向途径的组成部分,也发现在RV感染期间表达显著降低。这些miRNA的异位表达可以通过靶向Wnt信号通路的中间体来限制RV发病机理。miR-192家族和miR-181a能够通过靶向Wnt/β-连环蛋白途径抑制RV感染。该研究不仅强调了Wnt信号级联在RV感染中的作用,而且还表明miRNA可以协同地显著减少RV复制。因此,miR-192家族和miR-181a成为抗RV感染的前瞻性抗病毒药物.
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